ABSTRACT
An understanding of the kinetics of absorption, distribution, metabolism, and excretion (ADME) in preclinical and clinical species is the key to risk assessment of preclinical toxicology data for humans. Given that doses used in preclinical toxicity are greater than pharmacological doses by orders of magnitude, it is likely that nonlinear kinetics may occur as a consequence of high concentrations mediated saturation of absorption and/or clearance process that may lead to unexpected dose and/or species-specific toxicities. Classical compartment-based blood/plasma toxicokinetic models are often sufficient to meet the objectives; however, they are too simplistic to relate biochemical and physiological processes to the kinetics of drug ADME. To meet the deficiencies of classical models, physiologically based toxicokinetic models have been developed. These models have found great utility in describing the kinetics of tissue distribution of drugs under a variety of exposure and disease conditions. It is to be emphasized that there are excellent reviews available on this topic, and readers are encouraged to consult these very detailed reviews on pharmacokinetics and toxicokinetics (1,2, and references therein).
